Dr. Shakhnovich Receives NIH Grant to study Effect of Obesity on Pantoprazole Pharmacokinetics and Pharmacodynamics in Children
Valentina Shakhnovich, MD, Gastroenterology/Clinical Pharmacology, received a five-year $944,579 Mentored Patient-Oriented Research Career Development Award (K23) from the National Institutes of Health.
Dr. Shakhnovich’s study “Effect of Obesity on Pantoprazole Pharmacokinetics and Pharmacodynamics in Children” builds on her recently published findings, from two independent prospective investigations, that demonstrate reduced drug clearance and increased systemic exposure to the proton pump inhibitor (PPI) pantoprazole for obese children.
This finding means that children with obesity don’t always need higher doses of medications, at least not PPIs. Using intravenous pantoprazole as a model drug probe for the drug metabolizing pathway CYP2C19, Dr. Shakhnovich is now testing the hypothesis that increased fat in the liver underlies the observed reduction in PPI clearance and examining the impact this reduced clearance has on drug effect. This research represents the first step in developing individualized drug dosing recommendations currently lacking for children with obesity (1 in 5 children in the U.S.).
“Understanding of the biologic and physiologic mechanisms underlying altered drug metabolism and clearance is the first step toward developing accurate predictive models for optimizing the dose selection of PPIs, and other drugs commonly prescribed to children with obesity and related comorbidities,” she wrote.
As an outcome of the work proposed, Dr. Shakhnovich expects to generate a physiologically-based pharmacokinetic and pharmacodynamic computer tool to bridge the critical information gap regarding optimal dose selection of medications for obese children.
Children’s Mercy Kansas City is an independent, non-profit, 386-bed pediatric health system, providing over half a million patient encounters each year for children from across the country. Children’s Mercy is ranked by U.S. News & World Report in nine specialties. We have received Magnet® recognition five times for excellence in nursing services. In affiliation with the University of Missouri-Kansas City, our faculty of more than 800 pediatric specialists and researchers is actively involved in clinical care, pediatric research and educating the next generation of pediatricians and pediatric subspecialists. The Children’s Mercy Research Institute (CMRI) integrates research and clinical care with nationally recognized expertise in genomic medicine, precision therapeutics, population health and health care innovation. In 2021 the CMRI moved into a nine-story, 375,000-square-foot space emphasizing a translational approach to research in which clinicians and researchers work together to accelerate the pace of discovery that enhances care.